| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Iron deficiency (with or without anaemia) |
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| E.1.1.1 | Medical condition in easily understood language |
| Iron deficiency (with or without anaemia (low number of healthy red blood cells)) |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10022972 |
| E.1.2 | Term | Iron deficiency anaemia |
| E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10002062 |
| E.1.2 | Term | Anaemia iron deficiency |
| E.1.2 | System Organ Class | 100000012842 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the pharmacokinetics (PK) and iron uptake of Ferric Maltol (ST10) in children and adolescents (aged 10-17 years) after twice daily [BID] oral doses of 7.8 mg, 16.6mg or 30 mg for 9 days (Days 1 to 9) and a single morning dose on Day 10, through measurement of serum iron, transferrin saturation (TSAT) and plasma concentrations of maltol and maltol glucuronide. |
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| E.2.2 | Secondary objectives of the trial |
1.To assess the effect of 7.8 mg, 16.6 mg or 30 mg Ferric Maltol in children and adolescents (aged 10-17 years) after twice daily oral doses for 9 days (Days 1 to 9) and a single morning dose on Day 10, on serum transferrin, total and unsaturated iron binding capacity (TIBC, UIBC), ferritin, non-transferrin bound iron (NTBI); routine haematology indices, including absolute reticulocyte count, in blood.
2.To assess the safety and tolerability of 7.8 mg, 16.6 mg or 30 mg Ferric Maltol in children and adolescents (aged 10-17 years) after twice daily oral doses for 9 days (Days 1 to 9) and a single morning dose on Day 10, based upon vital signs, adverse events, concomitant medications, 12-lead ECG and clinical laboratory safety blood tests.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Ability to understand the information given in the Independent Ethics Committee (IEC) approved information sheet and consent form. The parent or guardian of the study subject must sign and date the informed consent and authorisation to use protected health information (PHI) in accordance with national and local subject privacy regulations prior to any study mandated procedure. The study participant will be asked to provide their assent to participate in the study using IEC approved assent forms
2.Willing and able to comply with study requirements.
3.Age ≥10 to ≤17 years at the time of informed consent and throughout duration of the study.
4.A current diagnosis of iron deficiency (with or without anaemia); iron deficiency defined by ferritin <30 µg/L, or ferritin <50 µg/L with transferrin saturation (TSAT) <20%, as measured by the central laboratory at the Screening visit (subjects with or without anaemia may be enrolled providing Hb is ≥8.5 g/dL as measured at the Screening visit).
5.Where appropriate, female subjects of childbearing potential must agree to use a reliable method of contraception until study completion and for at least 4 weeks following their final study visit. Reliable contraception is defined as a method which results in a low failure rate, i.e., less than 1% per year when used consistently and correctly.
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| E.4 | Principal exclusion criteria |
1.Has untreated or untreatable severe malabsorption syndrome e.g., untreated coeliac disease
2.Has received within 28 days prior to screening intramuscular or intravenous (IV) injection or administration of depot iron preparation.
3.Has received oral iron supplementation within 7 days prior to screening
4.Has received blood transfusion within 12 weeks prior to screening or is scheduled to have blood transfusion or donations during the study period.
5.Has concomitant disease that would significantly compromise iron absorption or absorbed iron utilisation such as swallowing disorders and/or extensive small bowel resection.
6.Has chronic renal disease (eGFR <30mL/min), as assessed at Screening based on serum creatinine and ethnicity
7.Known hypersensitivity or allergy to either the active substance or excipients of ferric maltol capsules.
8.Has a known contraindication for treatment with iron preparations , e.g., haemochromatosis, chronic haemolytic disease, sideroblastic anaemia, thalassemia, or lead intoxication induced anaemia.
9.Impaired liver function as indicated by alanine aminotransferase (ALT) or aspartate transaminase (AST)>2.0 times upper normal limit as measured at the Screening visit.
10.Active acute inflammatory disease including IBD flare or disease exacerbation, which in the opinion of the Investigator, is clinically significant.
11.Active chronic or acute infectious diseases requiring antibiotic treatment
12.Pregnant or breast feeding.
13.Concomitant medical conditions with extensive active bleeding, other than menstrual cycles; subjects who suffer from menorrhagia may be excluded at the Investigators discretion.
14.Scheduled or expected hospitalization and/or surgery during the course of the study
15.Participation in any other interventional clinical study within 28 days prior to screening.
16.Cardiovascular, liver, renal, hematologic, psychiatric, neurologic, gastrointestinal, immunologic, endocrine, metabolic, respiratory or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject.
17. Any other unspecified reason that, in the opinion of the Investigator or the Sponsor make the subject unsuitable for enrolment.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1.Population PK analysis of maltol and maltol glucuronide in plasma from PK samples collected on Day 1 (after first morning dose) and Day 10 (after last morning dose). Parameters to be derived and reported for each Ferric Maltol dose will be:
Cmax, Cave(0-6h), AUC(0-6h), AUC(0-inf) on Day 1 and Day 10, and ratios of Day 10/Day 1 for these parameters.
Tmax, half-life (t1/2).
Apparent systemic clearance (CL/F), apparent volume of distribution (V/F)
Descriptive statistics for plasma concentrations of maltol and maltol glucuronide by time of collection on Day 1 and Day 10 will also be presented, including Ctrough.
2.Descriptive and population PK analysis of serum iron and TSAT from PK samples collected on Day 1 and Day 10. Parameters to be derived and reported for each Ferric Maltol dose will be:
Change from pre-dose (Ctrough) to maximum post-dose (Cmax) value for serum iron and TSAT; Cave(0-6h).
Pre-dose adjusted Incremental AUC(0-6h) on Day 1 and Day 10 from a population PK analysis approach, and percentage change from Day 1 to Day 10.
Apparent systemic clearance (CL/F), apparent volume of distribution (V/F).
Descriptive statistics for serum iron and TSAT by time of collection on Day 1 and Day 10 will also be presented
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Sparse sampling; Pre-dose, 0.5-1 hr, 1-2 hr, 2-3 hr, 3-4 hr, 4-6 hr on Day 1 and 10 |
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| E.5.2 | Secondary end point(s) |
1.Descriptive analysis of transferrin, TIBC, UIBC and ferritin concentrations from PK samples collected on Day 1 and Day 10.
2.Descriptive analysis of non-transferrin bound iron (NTBI) concentrations from PK samples collected on Day 1 and Day 10.
3.Descriptive analysis of haemoglobin concentration and absolute reticulocyte count from haematology samples collected at Screening and Day 10.
4.Treatment-emergent Adverse Events (AEs) will be summarised.
5.Treatment-emergent Serious Adverse Events (SAEs) will be summarised.
6.Treatment-emergent Adverse Events leading to premature discontinuation of study drug/PK assessments will be summarised.
7.Clinical laboratory safety blood results at Screening and Day 10 will be summarised.
8.Changes in vital signs and 12-lead ECG will be summarised.
9.Concomitant medications will be summarised. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Sparse sampling; Pre-dose, 0.5-1 hr, 1-2 hr, 2-3 hr, 3-4 hr, 4-6 hr on Day 1 and 10 |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Paediatric pharmacokinetic study to confirm paediatric doses for Phase III study |
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| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Different dose of same product |
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| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
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